1. Field of the Invention
The present invention relates to a method for accelerating the percutaneous absorption of metoclopramide (hereafter often merely MCP for brevity).
2. Description of the Prior Art
Drugs are commonly administered to the skin or mucosal tissues to treat local problems and systemic administration of drugs is commonly accomplished by ingesting pills or by injections. However, recently attempts have been made to achieve systemic administration of drugs by topical applications to the skin or mucosal tissues. Such topical means of achieving systemic administration has the advantage that desired blood levels can be readily achieved and maintained so that duration of therapy can be readily controlled. Thus, side effects due to an overdose of the drug can be prevented. Also, metabolism due to a first pass through the liver and gastric disturbances, which are characteristic of certain drugs such as indomethacin when administered orally, can also be eliminated.
However, normal skin is relatively impermeable to most drugs in that desired blood levels of the therapeutic agent cannot be achieved by means of percutaneous absorption. The percutaneous absorption of drugs can, however, be enhanced by means of adjuvants or penetration enhancers.
One of the best known of such penetrating adjuvants is dimethyl sulfoxide, the use of which is described in detail in U.S. Pat. No. 3,551,554 Herschler et al.
British Pat. No. 1,504,302 Brooker et al deals with sedative methods and compositions and discloses the administration of sedatives by applying to the skin of a non-human animal a sedating amount of one or more sedative compounds in various penetrating adjuvants such as hydrocarbons such as aromatic hydrocarbons or paraffins, halogenated aliphatic hydrocarbons, ketones, esters, ethers, alcohols, amides or sulfones.
U.S. Pat. No. 4,202,888 Eckert et al discloses absorbable pharmaceutical compositions comprising at least one cardiac glycoside distributed in a vehicle comprising an absorption-enhancing amount of at least a partial glyceride of a fatty acid of medium chain length.
U.S. Pat. No. 3,472,931 Stoughton relates to percutaneous absorption using lower alkyl amides, and exemplifies binary systems which comprise dimethylacetamide and ethanol, dimethyl acetamide and isopropyl alcohol and dimethylacetamide and isopropyl palmitate.
U.S. Pat. No. 3,969,516 Stoughton discloses compositions for the treatment of acne which broadly can include "conventional formulating ingredients" including materials which enhance the percutaneous absorption of antibiotics of the lincomycin family, e.g., N-lower alkyl 2-pyrrolidones. Stearyl alcohol is used in the examples. This is a solid at 38.degree. C. and would be inoperable in the present inventions.
U.S. Pat. No. 3,989,816 Rajadhyakshn discloses percutaneous absorption systems for pyrrolidone-type compounds, including, e.g., in Example 3 isopropyl myristate without any disclosure of the purpose thereof. While stearyl and cetyl alcohol are disclosed, these are solids at 38.degree. C. and are inoperable in the present invention. Further, the pyrrolidone-type compounds used in the examples have a C.sub.8 group corresponding to R.sub.5 of the solvents of the present invention which renders such useless in the present invention.
U.S. Pat. No. 4,017,641 DiGiulio discloses skin moisturizing compositions (emulsions) containing 2-pyrrolidinone. Stearyl and cetyl alcohol (solids at 38.degree. C.) are disclosed as useful components. DiGiulio also broadly discloses the use of certain esters of lanolin fatty acids, certain straight chain fatty alcohols or straight chain fatty alcohols.
European Patent Application 0043738 discloses binary percutaneous administration systems which comprise a monoglyceride, a diol or a diol ether in combination with a second component such as an alcohol, ester, amide or the like.
The present invention involves multicomponent carrier systems for the percutaneous administration of metoclopramide which differ from the systems disclosed in the above prior art.